Characterization of baseline polybacterial versus monobacterial infections in three randomized controlled bacterial conjunctivitis trials and microbial outcomes with besifloxacin ophthalmic suspension 0.6.

BACKGROUND/PURPOSE: To date, studies examining polymicrobial infections in ocular disease have mostly been limited to keratitis or endophthalmitis. We characterized polybacterial infections compared to monobacterial infections in prior clinical studies evaluating besifloxacin ophthalmic suspension 0.6% for the treatment of bacterial conjunctivitis and report on associated microbiological outcomes. METHODS: In this post-hoc analysis, microbiological data for subjects with conjunctivitis due to one or more than one bacterial species in three previous studies (two vehicle-, one active-controlled) of besifloxacin were extracted. Bacterial species identified at baseline were deemed causative if their colony count equaled or exceeded species-specific prespecified threshold criteria. In subjects with polybacterial infections, the fold-increase over threshold was used to rank order the contribution of individual species. Baseline pathogens and their minimum inhibitory concentrations (MICs) for common ophthalmic antibiotics were compared by infection type, as were microbial eradication rates following treatment with besifloxacin. RESULTS: Of 1041 subjects with culture-confirmed conjunctivitis, 17% had polybacterial and 83% had monobacterial conjunctivitis at baseline. In polybacterial compared to monobacterial infections, Haemophilus influenzae and Streptococcus pneumoniae were identified less frequently as the dominant infecting species (P = 0.042 and P<0.001, respectively), whereas Streptococcus mitis/S. mitis group was identified more frequently as dominant (P<0.001). Viral coinfection was also identified more frequently in polybacterial infections (P<0.001). Staphylococcus aureus was the most common coinfecting species in polybacterial infections and the second most common dominant species in such infections. With few exceptions, MICs for individual species were comparable regardless of infection type. Clinical microbial eradication rates with besifloxacin were high regardless of infection type (P≤0.016 vs vehicle at follow-up visits). CONCLUSIONS: Approximately one in five subjects with bacterial conjunctivitis are infected with more than one bacterial species underscoring the need for a broad-spectrum antibiotic for such infections. Besifloxacin treatment resulted in robust eradication rates of these infections comparable to monobacterial infections. TRIAL REGISTRATION: NCT000622908, NCT00347932, NCT00348348.

Neisseria sicca: A Rare Cause of Bacterial Conjunctivitis.

BACKGROUND Neisseria-associated conjunctivitis is a rare cause of bacterial conjunctivitis in adults, with Neisseria gonorrhoeae as the primarily identified infectious strain. Here, we present a rare case of bacterial conjunctivitis due to Neisseria sicca in a 34-year-old immunocompetent man with no prior medical or ocular history. CASE REPORT A 34-year-old man with no significant past medical or ocular history presented with a 3-day history of left periorbital edema, ocular pain, and copious purulent discharge. Bacterial conjunctivitis was suspected due to the rapidity of onset and purulence. Peripheral corneal thinning was identified. Preliminary culture results showed gram-negative diplococci, and the patient was treated for gonococcal infection. Final cultures identified Neisseria sicca, a rarely pathogenic strain of Neisseria species. CONCLUSIONS This is the second reported case of Neisseria sicca-associated conjunctivitis, and the first reported case to have corneal involvement. Neisseria sicca, while typically non-pathogenic, may manifest as conjunctivitis in immunocompetent hosts with a low-risk sexual history.

Antibiotic resistance among bacterial conjunctival pathogens collected in the Antibiotic Resistance Monitoring in Ocular Microorganisms (ARMOR) surveillance study.

The Antibiotic Resistance Monitoring in Ocular Microorganisms (ARMOR) surveillance study evaluates in vitro antibiotic resistance among Staphylococcus aureus, coagulase-negative staphylococci (CoNS), Streptococcus pneumoniae, Pseudomonas aeruginosa, and Haemophilus influenzae isolates from ocular infections. Here we report resistance rates and trends among conjunctival-sourced ocular isolates collected across the US from 2009 through 2016. A total of 1198 conjunctival isolates (483 S. aureus, 305 CoNS, 208 H. influenzae, 118 S. pneumoniae, and 84 P. aeruginosa) were collected from patients with presumed bacterial conjunctivitis from 57 sites across 40 states. A large proportion of staphylococci demonstrated resistance to oxacillin and azithromycin, while resistance was low against the majority of antibiotics tested for S. pneumoniae, P. aeruginosa, and H. influenzae. Multidrug resistance (≥3 antibiotic classes) was found in 30.2% of S. aureus and 39.0% of CoNS isolates, and methicillin resistance more than doubled the rate of multi-drug resistance (methicillin-resistant S. aureus [MRSA], 76.5%; methicillin-resistant CoNS isolates, 72.8%). There was a pattern of increasing mean percent resistance with increasing age by decade of life among S. aureus, MRSA, and CoNS (P≤0.038). Over the eight-year study period, there were small yet significant decreases in resistance rates among S. aureus to azithromycin, ciprofloxacin, tobramycin, trimethoprim, and oxacillin (P≤0.003), and among CoNS and P. aeruginosa (both P<0.05) to ciprofloxacin. These data indicate that antibiotic resistance is high, but did not increase, among conjunctival-sourced isolates collected in the US from 2009 through 2016. For certain antibiotic/pathogen combinations, there was a trend of decreased resistance, including a decrease in oxacillin resistance among S. aureus.

A novel case of chronic conjunctivitis in a 58-year-old woman caused by Raoultella.

A 58-year-old woman presented to eye emergency with a chronic conjunctivitis which was diagnosed by laboratory microbiological testing to be due to the environmental pathogen Raoultella planticola. The organism was sensitive to Chloramphenicol and the patient made a rapid recovery on these drops. This is the first report of this organism infecting the eye.

Pasteurella canis and Granulicatella adiacens conjunctivitis outbreak resistant to empirical treatment in a child welfare agency.

PURPOSE: To investigate pathogens associated with bacterial conjunctivitis resistant to the empirical treatment and their antibiotic resistance in a child welfare agency. METHODS: Twenty-eight eyes in 14 children with a median age of 3 months with conjunctivitis resistant to the empirical treatment were included in this study. Samples were taken three times from the inferior fornix in both eyes using cotton swabs, cultured onto chocolate and blood agar, and prepared for Gram staining. Antibiograms were evaluated according to the Clinical and Laboratory Standards Institute criteria by disc diffusion method. RESULTS: The conjunctival culture positivity rate was 35.7% in eyes with conjunctivitis resistant to the empirical treatment. The most common isolated bacteria were Pasteurella canis (25%), penicillin-nonsusceptible Streptococcus pneumoniae (7.1%), and Granulicatella adiacens (3.6%). According to culture results, ophthalmic solutions of vancomycin (50 mg/mL) or gentamicin (30 mg/mL) were applied in eyes with positive conjunctival culture. Previously applied multiple treatments were stopped in eyes with negative conjunctival culture. All eyes improved clinically during follow-up. CONCLUSION: Because unusual pathogens may cause a conjunctivitis outbreak, physicians should not insist on empirical treatment. Taking conjunctival culture and antibiotic switching according to antibiogram may be helpful.

Topical ophthalmic moxifloxacin elicits minimal or no selection of fluoroquinolone resistance among bacteria isolated from the skin, nose, and throat.

PURPOSE: To investigate whether moxifloxacin therapy of bacterial conjunctivitis in children changes the moxifloxacin susceptibility of bacterial isolates in eyes, cheeks below eyes, nares, and throat. METHODS: Patients (age: 1 to 12 years, n = 105) with bacterial conjunctivitis were treated topically with moxifloxacin three times a day for 7 days. Gender- and age-matched subjects with normal eyes (age: 1 to 12 years, n = 57) served as the control group. Microbiological specimens were collected on days 1 (prior to therapy), 8 (1 day after end of therapy), and 42 (follow-up). Specimens were processed to recover total bacteria and bacteria that grew on fluoroquinolone-selective media. Bacteria were identified to the species level and susceptibility to moxifloxacin and selected other antibiotics determined. RESULTS: The primary pathogens recovered from the infected eyes on day 1 before therapy were Haemophilus influenzae, Streptococcus pneumoniae, and Staphylococcus aureus. None of the pre-therapy isolates of H. influenzae and S. pneumoniae were resistant to moxifloxacin. Isolates of these two pathogenic species were also recovered primarily from the nose and eyes. Moxifloxacin-resistant S. aureus isolates (minimum inhibitory concentration 1.0 µg/mL or greater) were recovered from the nose and throat prior to topical dosing on day 1. However, there was no change in the frequency of moxifloxacin-resistant isolates of S. aureus following treatment with moxifloxacin. CONCLUSION: Treatment of conjunctivitis with topical ophthalmic moxifloxacin did not select for moxifloxacin resistance in H. influenzae, S. pneumoniae, or S. aureus in the eye or distal body sites.

The role of topical moxifloxacin, a new antibacterial in Europe, in the treatment of bacterial conjunctivitis.

This article discusses current practice in the treatment of conjunctivitis and how the use of topical moxifloxacin can increase therapeutic effectiveness, reduce treatment failures and, consequently, be cost effective and reduce the societal burden of the disorder. Current practice and effectiveness data were derived from the literature. Data on healthcare utilization as a result of treatment failure were collected by survey and the cost of treatment was defined using national costings. A decision-analytic model to assess cost effectiveness was developed and the impact on the healthcare budget was calculated to define the health economic impact. Bacterial conjunctivitis represents a significant health problem and accounts for an estimated 1-1.5% of primary-care consultations. The disorder is highly contagious and causes a substantial healthcare and societal burden. Bacterial conjunctivitis is generally self-limiting, resolving within 1-2 weeks. However, the use of antibacterials significantly improves clinical and microbiological remission, shortens symptom duration, and enables more effective use of healthcare resources, compared with placebo. From a health economic perspective this benefits the healthcare system and society, since fewer healthcare resources are needed and the adult affected, or the parent/caregiver of the child affected, can return to full work capacity sooner, reducing loss of productivity. Treatment strategies vary significantly between countries. Most patients are first seen in primary care, where 'wait-and-see', lubrification and antiseptic or antibacterial treatment is provided. In Europe, when antibacterials are prescribed most general practitioners (GPs) prescribe a broad-spectrum topical antibacterial. The most commonly used drugs are chloramphenicol and fusidic acid, with fluoroquinolones rarely reported as first-line treatment by GPs. At the specialist (ophthalmologist) level, or for second-line treatment at the GP level, topical antibacterials are frequently used. However, in most countries, topical fluoroquinolones, particularly those recently approved by the European Medicines Agency, such as topical levofloxacin and topical moxifloxacin, are rarely used and instead are reserved for use as a last resort. In other parts of the world topical lomefloxacin, gatifloxacin and/or besifloxacin are also available. The strategy of using novel topical fluoroquinolones as a last resort reflects a belief that the use of topical fluoroquinolones may enhance the development of resistance, jeopardizing future availability of antibacterial treatment for ocular infections. In fact, most cases of bacterial resistance arise as a result of systemic treatment. Thus, this concern should not be extrapolated to topical use of fluoroquinolones, which results in antibacterial concentrations at the ocular surface that can significantly exceed mutant prevention concentrations. In addition, with products such as topical moxifloxacin, a dual-step mutation is required for resistance to emerge. Moxifloxacin restricts the selection of resistant mutants, meaning that emergence of resistance is unlikely. The strategy of not using the most effective fluoroquinolones such as topical moxifloxacin may lead to more patients with no improvement or worsening of symptoms, requiring re-intervention, additional examination and new treatment; these outcomes are defined as 'treatment failures'. Treatment failures cause an extra societal burden and increased costs due to the extra healthcare resources required (additional GP/specialist visits, laboratory tests, additional treatment, etc.). Compared with non-fluoroquinolones, topical moxifloxacin has a higher potency and faster in vitro 'speed-to-kill'. It has also been shown that, within the fluoroquinolone class, topical moxifloxacin and besifloxacin achieve the highest mean concentrations in conjunctival tissue, have the longest residence times and display favourable area under the concentration-time curve from time zero to 24 hours (AUC(24))/minimum inhibitory concentration ratio required to inhibit the growth of 90% of organisms (MIC(90)) and thus favourable pharmacokinetic/pharmacodynamic characteristics. This can result in reduced time-to-cure and a lower number of treatment failures, leading to better disease management and a healthcare-economic benefit arising from the associated reduction in utilization of healthcare resources. The high potency and mean concentration in conjunctival tissue combined with the long residence time of topical moxifloxacin enables a dosing strategy of three times daily for 5 days. Topical moxifloxacin is also the first ophthalmic antibacterial in Europe provided as a multidose, self-preserved, topical solution, thus avoiding the risk of benzalkonium chloride preservative-related allergic reactions and swelling. In addition, topical moxifloxacin has a near neutral pH (6.8) and is well tolerated by patients. Given the characteristics of the novel topical fluoroquinolones, a change in the healthcare treatment strategy for acute infectious conjunctivitis is to be recommended. Topical application of fluoroquinolones, such as moxifloxacin multidose self-preserved solution, should be considered earlier in the treatment path for conjunctivitis. Notwithstanding the premium price attached to this novel topical antibacterial, use of topical moxifloxacin for bacterial conjunctivitis can be cost effective and even generate total healthcare budget savings by reducing both the costs of managing treatment failures and the use of clinicians' time to manage such failures.

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.

Besifloxacin: a topical fluoroquinolone for the treatment of bacterial conjunctivitis.

BACKGROUND: Besifloxacin is a topical ophthalmic fluoroquinolone that was approved by the US Food and Drug Administration (FDA) in May 2009 for the treatment of bacterial conjunctivitis caused by susceptible bacterial strains. OBJECTIVE: This article provides an overview of the pharmacology, clinical efficacy, and tolerability of ophthalmic besifloxacin when used for the treatment of bacterial conjunctivitis. METHODS: Relevant reports pertaining to the pharmacology, efficacy, and tolerability of besifloxacin were identified through a search of MEDLINE (1985-December 2009) and International Pharmaceutical Abstracts (1985-December 2009) using the terms besifloxacin, BOL-303224-A, ophthalmic fluoroquinolones, and bacterial conjunctivitis. Additional publications were identified by reviewing the reference lists of identified articles and searching the FDA Web site. RESULTS: Besifloxacin has potent in vitro inhibitory activity against most common ocular bacterial pathogens (MIC90 values generally < or =4 microg/mL), including Staphylococcus aureus, Streptococcus pneumoniae, and Haemophilus influenzae. In an ocular pharmacokinetic study in 64 healthy volunteers, the C(max) in tears (mean [SD], 610 [540] microg/mL) was reached 10 minutes after a single ocular instillation of besifloxacin; concentrations > or =1.6 microg/g of tear were sustained for at least 24 hours; and the elimination t(1/2) was ~3.4 hours. In a study in 24 patients with a clinical diagnosis of bilateral bacterial conjunctivitis, systemic exposure (C(max)) after administration of besifloxacin ophthalmic suspension 3 times daily for 5 days was <0.5 ng/mL. In 2 randomized, double-masked, vehicle-controlled clinical trials, besifloxacin ophthalmic suspension was well tolerated and significantly more efficacious than vehicle in achieving clinical resolution (73.3% vs 43.1%, respectively, in one of the studies [P < 0.001]; 45.2% vs 33.0% in the other [P = 0.008]) and microbial eradication (88.3% vs 60.3% [P < 0.001] and 91.5% vs 59.7% [P < 0.001], respectively). In a randomized, double-masked, parallel-group, noninferiority trial comparing besifloxacin ophthalmic suspension 0.6% with moxifloxacin ophthalmic solution 0.5%, besifloxacin was found to be noninferior to moxifloxacin (predefined cutoff for noninferiority = -15), with no significant differences in rates of clinical resolution (58.3% and 59.4%, respectively; 95% CI, -9.48 to 7.29) or microbial eradication (93.3% and 91.1%; 95% CI, -2.44 to 6.74). Besifloxacin was generally well tolerated in these clinical trials, with the most common (> or =1.5%) ocular adverse events being nonspecific conjunctivitis (2.6%), blurred vision (2.1%), bacterial conjunctivitis (1.8%), and eye pain (1.5%). The recommended dose of besifloxacin is 1 drop in the affected eye(s) 3 times daily (4-12 hours apart) for 7 days. CONCLUSION: Besifloxacin ophthalmic suspension 0.6% appeared to be well tolerated in the populations studied and was efficacious in the treatment of bacterial conjunctivitis caused by susceptible isolates.

Efficacy and safety of besifloxacin ophthalmic suspension 0.6% in children and adolescents with bacterial conjunctivitis: a post hoc, subgroup analysis of three randomized, double-masked, parallel-group, multicenter clinical trials.

BACKGROUND: Acute conjunctivitis is the most frequent eye disorder seen by primary care physicians and one that often affects children. Besifloxacin is a new topical fluoroquinolone, the first chlorofluoroquinolone, for the treatment of bacterial conjunctivitis. OBJECTIVE: To examine the efficacy and safety of besifloxacin ophthalmic suspension 0.6% in patients aged 1-17 years with bacterial conjunctivitis. METHODS: This was a post hoc analysis of a subgroup of pediatric patients aged 1-17 years who had participated in three previously reported, randomized, double-masked, parallel-group, multicenter, clinical trials evaluating the safety and efficacy of besifloxacin in the treatment of bacterial conjunctivitis. The studies were conducted in a community setting (clinical centers). All three clinical trials included children (aged > or = 1 year) with a clinical diagnosis of bacterial conjunctivitis in at least one eye, based on the presence at baseline of grade 1 or greater purulent conjunctival discharge and conjunctival injection, and pin-hole visual acuity of at least 20/200 in both eyes for verbal patients. Two trials were vehicle controlled; the third trial was comparator controlled (moxifloxacin hydrochloride ophthalmic solution 0.5% as base). In all studies, besifloxacin ophthalmic suspension 0.6% was administered as one drop in the affected eye(s) three times daily, at approximately 6-hourly intervals, for 5 days. The main outcome measures were clinical resolution and microbial eradication at visit 2 (day 4 +/- 1 in one study; day 5 +/- 1 in the other two studies) and visit 3 (day 8 or 9). Data from the two vehicle-controlled studies were combined for the assessments to provide greater statistical power. RESULTS: This analysis included 815 pediatric patients aged 1-17 years (447 with culture-confirmed bacterial conjunctivitis). Clinical resolution was significantly greater (p < 0.05) in the besifloxacin group than in the vehicle group at both visit 2 (53.7% vs 41.3%) and visit 3 (88.1% vs 73.0%). Similarly, microbial eradication was significantly higher with besifloxacin than with vehicle at visit 2 (85.8% vs 56.3%) and visit 3 (82.8% vs 68.3%). No significant differences in clinical resolution and microbial eradication were noted between besifloxacin and moxifloxacin. Besifloxacin was well tolerated, with similar incidences of adverse events in the besifloxacin, vehicle, and moxifloxacin groups. CONCLUSION: Besifloxacin ophthalmic suspension 0.6% was shown to be safe and effective for the treatment of bacterial conjunctivitis in children and adolescents aged 1-17 years.

Besifloxacin, a new ophthalmic fluoroquinolone for the treatment of bacterial conjunctivitis.

Besifloxacin is a new fluoroquinolone anti-infective developed for ophthalmic use. Besifloxacin ophthalmic suspension 0.6% (Besivance) was recently approved for the treatment of bacterial conjunctivitis. The objective of this article is to provide a comprehensive overview of microbiological, pharmacokinetic/pharmacodynamic and clinical studies with besifloxacin. Microbiological studies have demonstrated that besifloxacin has wide-spectrum and potent activity against common ocular pathogens, including Gram-negative and Gram-positive pathogens associated with bacterial conjunctivitis, and retained activity against fluoroquinolone-resistant staphylococci and multidrug-resistant strains. In preclinical and human studies, topically applied besifloxacin had a prolonged ocular concentration and minimal systemic exposure. In clinical studies, patients randomized to besifloxacin ophthalmic suspension 0.6% experienced significantly higher rates of clinical resolution and microbial eradication than patients randomized to vehicle. Besifloxacin ophthalmic suspension 0.6% was also found to be as effective and well tolerated as moxifloxacin ophthalmic solution 0.5%. The low minimum inhibitory concentrations and high attainment of pharmacodynamic targets with besifloxacin may contribute to a lower risk for the emergence of bacterial resistance, although further studies are needed. These data indicate that besifloxacin ophthalmic suspension 0.6% is an important new option for the treatment of bacterial conjunctivitis.

Efficacy and safety of besifloxacin ophthalmic suspension 0.6% compared with moxifloxacin ophthalmic solution 0.5% for treating bacterial conjunctivitis.

OBJECTIVE: To compare the clinical and antimicrobial efficacy of besifloxacin ophthalmic suspension 0.6% with that of moxifloxacin ophthalmic solution 0.5% for the treatment of bacterial conjunctivitis. DESIGN: Multicenter, randomized, double-masked, parallel-group, active-controlled, noninferiority study. PARTICIPANTS: Patients 1 year of age or older with clinical manifestations of bacterial conjunctivitis. METHODS: Eligible patients were randomized to either besifloxacin suspension or moxifloxacin solution, instilled in the infected eye(s) 3 times daily for 5 days, and participated in study visits on days 1, 5 (+/-1 day), and 8 (+1 day). Assessments included clinical evaluation of signs and symptoms, visual acuity, biomicroscopy, and culture of the infected eye(s) at each visit, as well as direct ophthalmoscopy on days 1 and 8. MAIN OUTCOME MEASURES: The primary efficacy end points were clinical resolution and microbial eradication of baseline bacterial infection on day 5 in patients with culture-confirmed bacterial conjunctivitis. Secondary end points included clinical resolution and microbial eradication on day 8, individual clinical outcomes, microbial and clinical outcomes by bacterial species, and safety. RESULTS: A total of 1161 patients (533 with culture-confirmed bacterial conjunctivitis) were randomized. Based on the 95% confidence interval (CI) of the difference, besifloxacin was noninferior to moxifloxacin for clinical resolution on day 5 (58.3% vs. 59.4%, respectively; 95% CI, -9.48 to 7.29) and day 8 (84.5% vs. 84.0%, respectively, 95% CI, -5.6% to 6.75%) and for microbial eradication on day 5 (93.3% vs. 91.1%, respectively, 95% CI, -2.44 to 6.74) and day 8 (87.3% vs. 84.7%; 95% CI, -3.32 to 8.53). There was no statistically significant difference between the 2 treatment groups for either efficacy end points on days 5 or 8 (P>0.05). Besifloxacin and moxifloxacin were well tolerated. The cumulative frequency of ocular adverse events was similar between treatments (12% and 14% with besifloxacin and moxifloxacin, respectively). However, eye irritation occurred more often in moxifloxacin-treated eyes (0.3% for besifloxacin vs. 1.4% for moxifloxacin; P = 0.0201). CONCLUSIONS: Besifloxacin ophthalmic suspension was non inferior to moxifloxacin ophthalmic suspension and provided similar safety and efficacy (clinical and microbiological) outcomes when used for the treatment of bacterial conjunctivitis. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

A multicenter comparison of polymyxin B sulfate/trimethoprim ophthalmic solution and moxifloxacin in the speed of clinical efficacy for the treatment of bacterial conjunctivitis.

PURPOSE: To compare the speed of clinical efficacy for two currently available topical antibiotics: polymyxin B sulfate/trimethoprim (polymyxin/trimethoprim) and 0.5% moxifloxacin ophthalmic solution. METHODS: Eighty-four eyes of 56 patients younger than 18 years with a clinical diagnosis of bacterial conjunctivitis were enrolled in this multicenter study. Patients were randomly assigned to receive either 1 drop of polymyxin/trimethoprim four times daily for 7 days or 1 drop of 0.5% moxifloxacin three times daily for 7 days. Ocular signs and symptoms were evaluated at baseline and 24 and 48 hours after the start of dosing. Microbiological cultures were collected at baseline and 48 hours. Patients rated ocular symptoms and adverse events on day 7 via telephone interview. Primary efficacy assessment included relief of all signs and symptoms of bacterial conjunctivitis. RESULTS: All patients but one completed all visits. At the 48-hour visit, complete resolution of ocular signs and symptoms was observed in 81% of the patients treated with moxifloxacin and 44% of the patients treated with polymyxin/trimethoprim (P = .001). No adverse events were reported. CONCLUSION: Moxifloxacin 0.5% administered three times daily is safe and cures bacterial conjunctivitis more effectively and significantly faster than polymyxin/trimethoprim dosed four times daily. The majority of patients were cured and symptom-free by 48 hours. Therefore, moxifloxacin is cost-effective and significantly more efficacious than polymyxin/trimethoprim in the speed by which it reduces the symptoms and disease transmission.

Microbiological efficacy of 3-day treatment with azithromycin 1.5% eye-drops for purulent bacterial conjunctivitis.

PURPOSE: Antibacterial efficacy of topically applied azithromycin 1.5% was compared with tobramycin 0.3% in a multicenter, randomized, investigator-masked study for the treatment of purulent bacterial conjunctivitis. METHODS: A total of 1043 adults and children received either azithromycin twice daily for 3 days (n=524) or tobramycin every 2 hours while awake for 2 days, then four times daily for 5 days (n=519). Conjunctival swabbing was taken at days 0, 3, and 9, using alginate swabs resuspended in a dissolution-transport medium, providing rapid and reproducible results. Cagle's criteria were used to define the pathogenicity level for each isolated bacterium. RESULTS: In the per-protocol set, the rate of bacteriologic resolution was 85.2% for azithromycin versus 83.8% for tobramycin on day 3, and 92.8% for azithromycin versus 94.6% for tobramycin on day 9. Azithromycin was demonstrated to be noninferior to tobramycin according to the 10% noninferiority margin. Although some bacteria were categorized as resistant to tested antibiotics, eradication was observed (for azithromycin: Acinetobacter, Enterobacteriaceae, Pseudomonas), highlighting the specific pharmacokinetics/pharmacodynamics of the ocular route. CONCLUSIONS: In total, topical therapy with azithromycin 1.5% administered only twice daily for 3 days effectively eradicates most pathogenic bacteria associated with bacterial conjunctivitis. These microbiologic results are in accordance with the observed clinical outcome. This new anti-infective product has the advantage of a short treatment course which could lead to an improvement in patient compliance.

Clinical cure of bacterial conjunctivitis with azithromycin 1%: vehicle-controlled, double-masked clinical trial.

PURPOSE: To analyze the effect of azithromycin 1% ophthalmic solution in DuraSite (InSite Vision, Inc, Alameda, California, USA) on bacterial conjunctivitis. DESIGN: Prospective, randomized, vehicle-controlled, parallel-group, double-masked multicenter clinical study. METHODS: Eligible male or female participants with a clinical diagnosis of acute bacterial conjunctivitis were randomized to either 1% azithromycin in DuraSite or vehicle for five days. Infected eyes were dosed twice daily on days 1 and 2 and once daily on days 3 through 5. Conjunctival cultures were obtained at baseline, visit 2 (day 3 or 4), and visit 3 (day 6 or 7). The primary end point was clinical resolution of signs and symptoms (rating of zero on ocular discharge, bulbar and palpebral injection) at visit 3. Efficacy measures were clinical resolution and bacterial eradication as evaluated in the per-protocol population. Safety was assessed by adverse events, slit-lamp findings, and ophthalmoscopy. RESULTS: Two hundred and seventy-nine participants (n = 130, 1% azithromycin in DuraSite; n = 149, vehicle), age one to 96 years, were evaluated for efficacy. Clinical resolution with azithromycin ophthalmic solution was statistically significant compared with that of vehicle (P = .030) at visit 3. Bacterial eradication rates with azithromycin ophthalmic solution reached 88.5% at visit 3 (P < .001) and included some pathogens resistant to azithromycin in vitro. Overall, adverse event rates were similar in both treatment groups. CONCLUSIONS: Azithromycin 1% ophthalmic solution in DuraSite showed statistically significant differences in clinical resolution and bacterial eradication rates when compared with vehicle. Because it was well tolerated in this population, it may be a viable treatment option for children and adults with bacterial conjunctivitis.

The pharmacodynamic properties of azithromycin in a kinetics-of-kill model and implications for bacterial conjunctivitis treatment.

INTRODUCTION: Antibiotics have traditionally been classified as bactericidal or bacteriostatic. Azithromycin belongs to the parent class of macrolides that are characteristically bacteriostatic. Some evidence suggests that this molecule demonstrates bactericidal kill and has concentration-dependent effects. This study tests the hypothesis that azithromycin demonstrates a bactericidal, concentration-dependent antibiotic effect at concentrations corresponding to and exceeding published tear and conjunctival levels. METHODS: The antibacterial activity of different concentrations of azithromycin 1% in DuraSite(R) (AzaSite(R); Inspire Pharmaceuticals Inc, Durham, NC, USA) was evaluated using a kinetics-of-kill model. Recent conjunctivitis isolates of Staphylococcus aureus, Streptococcus pneumoniae or Haemophilus influenzae were exposed to four concentrations of azithromycin (100, 250, 500 and 750 microg/ml). Starting concentrations were similar to the maximum concentrations (Cmax) that have been demonstrated in conjunctiva (83 microg/g) and tears (288 microg/ml) following topical ocular administration. The percentage of surviving bacteria at 30 and 60 minutes following exposure to each concentration were determined. RESULTS: Azithromycin failed to demonstrate bactericidal activity (i.e. a 3-log reduction in surviving bacteria) against S. aureus, S. pneumoniae or H. influenzae. Furthermore, the rate and extent of antibacterial activity with azithromycin did not change with higher concentrations, even at the highest tested concentration of 750 microg/ml. CONCLUSION: Similar to the parent macrolide class, azithromycin demonstrates bacteriostatic activity against common conjunctival pathogens up to the maximum tested concentration of 750 microg/ml (i.e. 2.6-times and 9-times published Cmax tear and conjunctival concentration, respectively). Azithromycin's bacteriostatic effects and prolonged elimination half-life will likely lead to a corresponding increase in the emergence of macrolide-resistant isolates.

Comparison of azithromycin and moxifloxacin against bacterial isolates causing conjunctivitis.

OBJECTIVE: To examine in vitro resistance to azithromycin and moxifloxacin in bacterial conjunctivitis isolates. METHODS: MIC90s (Minimum Inhibitory Concentration) and resistance rates to azithromycin and moxifloxacin were determined based upon microtiter broth dilution and/or antimicrobial gradient test strips in a multicenter phase III study and confirmed externally. RESULTS: The most common isolates collected from bacterial conjunctivitis patients in the phase III study were Haemophilus influenzae (40.6%), followed by Staphylococcus epidermidis (19.3%), Propionibacterium acnes (17.3%), Streptococcus pneumoniae (16.8%), and Staphylococcus aureus (0.06%). MIC90s for all of these organisms were well below established resistance breakpoints for moxifloxacin, indicating no bacterial resistance. On the other hand, the MIC90 for H. influenzae was 3-fold higher than the resistance breakpoint for azithromycin, > or = 128-fold higher for S. epidermidis, 16-fold higher for S. pneumoniae and > or = 128-fold higher for S. aureus, indicating moderate to very high bacterial resistance to azithromycin. CONCLUSIONS: Resistance to azithromycin is more common than resistance to moxifloxacin in clinical isolates causing bacterial conjunctivitis.

A case of vancomycin-resistant enterococcus conjunctivitis and its clinically successful topical treatment.

PURPOSE: To describe what is, to our knowledge, the first documented case of vancomycin-resistant enterococcus (VRE) conjunctivitis and its successful topical treatment. METHODS: A 77-year-old white man with end-stage multiple myeloma was hospitalized for congestive heart failure and pneumonia. During hospitalization, the patient developed conjunctivitis. Cultures of the eye were directly plated into several media. The bacterium was tested for antibiotic minimum inhibitory concentration (MIC) with the Clinical and Laboratory Standards Institute (CLSI) method. RESULTS: Culture of the affected eye grew Enterococcus faecalis resistant to vancomycin. Topical treatment with moxifloxacin 0.5% (Vigamox; Alcon, Ft. Worth, TX) resulted in clinical resolution despite a MIC showing resistance. CONCLUSION: Clinical resolution of VRE conjunctivitis was shown with topical moxifloxacin therapy in this case. At the same time, we suggest the use of combined topical and systemic therapy for treatment of VRE in immunocompromised patients.