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Purpose/Aims: This study assessed the efficacy and safety of brimonidine tartrate ophthalmic solution, 0.025% for treating ocular redness in adult subjects. Materials and Methods: This was a single-center, double-masked, randomized, vehicle-controlled, parallel-group study in subjects ≥40 years, with ocular redness. Subjects were randomized 2:1 to brimonidine or vehicle, instilled QID for four weeks. Subjects completed four visits, the last occurring one week after treatment discontinuation. The investigator assessed ocular redness on a scale of 0–4 pre-instillation and 5–240 minutes post-instillation on Day 0, pre-instillation and 5 minutes post-instillation on Days 14 and 28, and on Day35; subjects assessed redness in diaries throughout the 28-day treatment period and following treatment discontinuation. Safety assessments included adverse events (AEs), rebound redness on treatment discontinuation, comprehensive ophthalmic exams, and vital signs. Drop comfort was assessed upon instillation, and 30 seconds and 1 minute post-instillation at Day 0. Results: Fifty-seven subjects (brimonidine, n = 38; vehicle, n = 19) were randomized. Investigator-assessed ocular redness was significantly reduced with brimonidine across the entire post-instillation time period (overall treatment difference: −1.37;P < 0.0001) and at all individual time points (P < 0.0001). Subject-assessed ocular redness was also significantly lower with brimonidine (P ≤ 0.0005). No tachyphylaxis was evident. There were few ocular AEs, all mild to moderate in severity, and no redness rebound was observed upon brimonidine discontinuation. There were no effects on any safety measures, and both brimonidine and its vehicle were reported to be very comfortable. Conclusions: Brimonidine 0.025% appeared safe, well tolerated, and reduced ocular redness for at least 4 hours. No tachyphylaxis or rebound redness upon treatment discontinuation was observed. [ABSTRACT FROM PUBLISHER]

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]

Introduction: Previous work has shown that besifloxacin, an 8-chloro-fluoroquinolone, has more potent activity against gram-positive pathogens than moxifloxacin and gatifloxacin, which carry an 8-methoxy group. This study was conducted to determine the contribution of the R7 and R8 substituent to fluoroquinolone antibacterial activity. Materials and methods: Besifloxacin, moxifloxacin, gatifloxacin, their R8 structural analogs, and ciprofloxacin were tested against representative isolates of various gram-positive and gram-negative species and previously characterized fluoroquinolone-resistant mutants of Staphylococcus aureus. Minimum inhibitory and minimum bactericidal concentrations were determined according to Clinical and Laboratory Standards Institute (CLSI) guidelines. Reserpine was used to determine the effect of efflux pumps on antibacterial activity. Results: In general, exchanging the R8 residue in besifloxacin slightly reduced the molecule's potency, while introducing an 8-chloro group in moxifloxacin increased its potency. A similar change in gatifloxacin had little to no effect. Substituting the R8 residues did not increase the susceptibility to the efflux pump inhibitor reserpine or result in a loss of bactericidal activity. In contrast, the positive control, ciprofloxacin, was shown to be a substrate for reserpine and lost bactericidal activity against some fluoroquinolone-resistant isolates of S. aureus. Conclusion: The data presented here show that, depending on the R7 substituent, replacing an 8-methoxy group with an 8-chloro substituent can improve potency or can have little-to-no effect. These findings highlight the importance of the interplay between the R7 and R8 substituents in determining antibacterial potency. [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: Methicillin-resistant Staphylococcus aureus (MRSA) strains are commonly classified as hospital-acquired (HA) or community-acquired (CA). Typical HA-MRSA isolates are characterized by multidrug resistance and the SCC mec type II cassette, while CA-MRSA isolates are generally susceptible to more drug classes, are often of SCC mec type IV, and frequently carry the Panton-Valentine leukocidin (PVL) genes. This study determined the presence of traits characteristic for CA and HA strains in ocular MRSA isolates. Materials and Methods: Fifty-six recent ocular isolates, consisting of 40 MRSA and 16 methicillin-susceptible Staphylococcus aureus (MSSA) comparator strains, were characterized. Minimum inhibitory concentration (MIC) testing was done according to current Clinical and Laboratory Standards Institute guidelines. Detection of the PVL encoding genes and determination of the SCC mec type was done by polymerase chain reaction (PCR), while spa typing and cluster analysis was performed following DNA sequencing. Results: Of the 38 typeable MRSA isolates, 22 were of SCC mec type II and 16 were of SCC mec type IV. All SCC mec type II isolates were multidrug-resistant, lacked the PVL genes, and were of spa type t002 or closely related spa types. In contrast, the SCC mec type IV isolates were resistant to fewer classes of antimicrobial agents, often possessed the PVL genes (75.0%), and were of spa type t008 or closely related spa types. Conclusions: While the majority of ocular MRSA strains in this study fit the classical profile of HA- and CA-MRSA, some CA-MRSA isolates exhibited higher levels of antimicrobial resistance, which should be of particular concern to eye-care professionals. Furthermore, the apparent association of spa types and SCC mec types observed here warrants further investigation and suggests that spa typing may be useful in future HA- and CA-MRSA characterization studies. [ABSTRACT FROM AUTHOR]

Purpose: To study the efficacy of topical administration of gatifloxacin (0.3%), moxifloxacin (0.5%) ophthalmic solutions, and besifloxacin (0.6%) ophthalmic suspension as prophylaxis and treatment of pneumococcal endophthalmitis. Methods: Four groups of New Zealand white rabbits were topically treated with gatifloxacin, moxifloxacin, besifloxacin, and phosphate-buffered saline (PBS) at the following time points: 60, 45, 30, and 15 min before infection, immediately after infection, and then 6, 12, 18, and 24 h postinfection. Penicillin-resistant Streptococcus pneumoniae (PRSP; 106 colony-forming unit [CFU] in 50 μL) was injected into the aqueous humor of each eye. The clinical severity of the eyes was assessed by 2 masked observers 24 h postinfection. Aqueous and vitreous samples were collected, diluted, and plated to determine recovered CFU. Results: Fluoroquinolone-treated eyes had significantly lower clinical scores and bacteria recovered from the aqueous humor than the PBS-treated eyes. There was no difference, however, among the fluoroquinolone-treated groups. In contrast, none of the fluoroquinolones reduced the number of bacteria recovered (CFU) from the vitreous humor. Conclusions: Besifloxacin is as effective as moxifloxacin and gatifloxacin in a rabbit model for topical prophylaxis and treatment of PRSP-induced endophthalmitis. [ABSTRACT FROM AUTHOR]