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Purpose/Aim: Bacterial infections of the ocular surface are commonly treated empirically with broad spectrum antibiotics. Due to concerns over increasing antibiotic resistance, we evaluated current susceptibility patterns of the ocular bacterial pathogens in Europe. Materials and methods: Non-consecutive ocular isolates ofStaphylococcus aureus, coagulase-negative staphylococci (CoNS),Streptococcus pneumoniae, Haemophilus influenzae, andPseudomonas aeruginosawere collected in 2011 from centers in France, Germany, Italy, Poland, Slovak Republic, Spain, and the United Kingdom. Centers were asked to provide similar numbers of methicillin-susceptible and -resistant staphylococcal isolates. Minimum inhibitory concentrations were determined for fluoroquinolones (besifloxacin, ciprofloxacin, moxifloxacin), aminoglycosides (tobramycin, gentamicin, netilmicin), oxacillin, chloramphenicol and erythromycin. Isolates were categorized as susceptible, intermediate, or resistant according to European Committee on Antimicrobial Susceptibility Testing (EUCAST) criteria. Results: A total of 741 ocular isolates were obtained. Antibiotic resistance rates depended not only on the antibiotic and species, but also varied greatly by the country of origin. Resistance to ciprofloxacin, tobramycin, erythromycin, and to a lesser extent, chloramphenicol, was a concern for all staphylococci. Multidrug resistance was common among methicillin-resistantS. aureus(MRSA) and MRCoNS and isolates ofS. pneumoniae, H. influenzae, andP. aeruginosawere frequently non-susceptible to erythromycin, beta-lactams, and ciprofloxacin/tobramycin, respectively. Resistance rates showed substantial differences among the seven countries tested. Fluoroquinolones and aminoglycosides showed differences in antibacterial potency and resilience toward the antibiotic resistance mechanisms. Conclusions: Methicillin-resistant staphylococcal isolates were frequently non-susceptible to a multitude of other antibiotics, making MRSA and MRCoNS a potentially significant concern. The broad range of resistance rates observed across Europe in this study confirms the importance of considering current local resistance patterns when antibacterial agents are chosen for empiric management of ocular infections. [ABSTRACT FROM AUTHOR]

Background: Besifloxacin ophthalmic suspension 0.6 % (Besivance ®; Bausch & Lomb, Rochester, NY, USA) was approved by the FDA in 2009 for the treatment of bacterial conjunctivitis, with a recommended 7-day dosing regimen. Objective: The objective of this study was to compare the safety of besifloxacin ophthalmic suspension 0.6 %, administered three times a day for 7 days, with that of its vehicle. Methods: This randomized, multicenter, double-masked, vehicle-controlled, parallel-group study involved 518 patients ≥1 year of age with a clinical diagnosis of bacterial conjunctivitis. Patients were randomized 2:1 to treatment with besifloxacin 0.6 % ophthalmic suspension or vehicle, one drop in the infected eye(s) TID for 7 days. Main outcomes included the incidence and types of adverse events reported by the subject or observed by the investigator at each study visit. Results: Thirty-one ocular treatment-emergent adverse events (TEAEs) were reported by 28 subjects in the study eye; 19 occurred in 17/344 (4.9 %) besifloxacin patients, and 12 occurred in 11/170 (6.5 %) vehicle patients ( p = 0.5362). Only two ocular events (mild instillation site reaction, one case in each group) were considered “definitely related” to study treatment. One event of self-limited dysgeusia in the besifloxacin group was considered definitely related to treatment; there were no other nonocular TEAEs considered related to treatment. There were no serious adverse events, and other safety outcomes (visual acuity, biomicroscopy, ophthalmoscopy) were unremarkable. Conclusion: These findings indicate that besifloxacin ophthalmic suspension 0.6 % is safe in patients aged 1 year and older when used TID for 7 days. [ABSTRACT FROM AUTHOR]

Background: The impact of mutations in DNA gyrase and topoisomerase IV on minimum inhibitory concentrations (MICs) was investigated to better understand why besifloxacin has a higher potency against Staphylococcus aureus when compared to other fluoroquinolones, which was especially pronounced against ciprofloxacin-resistant isolates. Methods: MICs were determined for 52 clinical isolates against besifloxacin, moxifloxacin, gatifloxacin, ciprofloxacin, and levofloxacin. The genes encoding GyrA, GyrB, ParC, and ParE were sequenced and the potential impact of mutations assessed in light of recent structural data. Results: For all fluoroquinolones tested, the MICs increased with the number of mutations in the quinolone resistance-determining regions. However, this increase was the smallest for besifloxacin and the largest for ciprofloxacin and levofloxacin. In addition to the commonly observed mutations in ParC and GyrA, more unusual mutations in ParE, such as Asp-432→His or Pro-585→Ser, were also detected. Conclusions: Compared to earlier fluoroquinolones, the higher potency of besifloxacin suggests that the drug's unique combination of a 7-azepinyl ring and an 8-chloro-substituent results in unique interactions with DNA gyrase and topoisomerase IV. Copyright © 2011 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Purpose: To determine the antibacterial susceptibility profile of bacterial pathogens from ocular infections against relevant aminoglycoside, β-lactam, cephalosporin, chloramphenicol, fluoroquinolone, glycopeptide, lincosamide, and macrolide antibacterial agents. Design: Laboratory investigation. Methods: Isolates from patients with bacterial eye infections were collected prospectively by 34 institutions across the United States and were submitted to a central laboratory for inclusion in the Antibiotic Resistance Monitoring in Ocular micRorganisms (ARMOR) study. Minimum inhibitory concentrations were determined by microbroth dilution for 200 Staphylococcus aureus (S. aureus), 144 coagulase-negative staphylococci, 75 Streptococcus pneumoniae (S. pneumoniae), 73 Haemophilus influenzae (H. influenzae), and 100 Pseudomonas aeruginosa (P. aeruginosa) isolates. Results: A large proportion of S. aureus and coagulase-negative staphylococci isolates were resistant to oxacillin/methicillin, azithromycin, or fluoroquinolones; 46.5% of S. aureus, 58.3% of coagulase-negative staphylococci, 9.0% of P. aeruginosa, and 9.3% of pneumococcal isolates were nonsusceptible to 2 or more antibacterial drug classes. Only 2.7% of H. influenzae isolates were nonsusceptible to 1 of the agents tested. Methicillin-resistant staphylococci were statistically more likely (all P < .0038) also to be resistant to fluoroquinolones, aminoglycosides, and macrolides. Conclusions: Resistance to 1 or more antibiotics is prevalent among ocular bacterial pathogens. Current resistance trends should be considered before initiating empiric treatment of common eye infections. [ABSTRACT FROM AUTHOR]

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. [Copyright &y& Elsevier]